Many fermentations are carried out in batch or continuously stirred tank reactors which are supplied with air or oxygen by means of spargers. Increased oxygen transfer rates are usually obtained by breaking up the bubbles and distributing them by means of an impeller. Bubble sizes are typically one millimeter or larger. Organism growth or product formation is often hampered by the formation of stagnant layers of foam that form on the top of the fermentation broth. See for example U.S. Pat. No. 3,846,246, Midorikawa et al. Typically, mass transfer in these systems is at the expense of energy.
Tower fermentors are also commonly used with large quantities of air sparged from the bottom of the apparatus to provide both aeriation, mixing and in some cases, improved heat transfer. The fermentor may be divided into two parts, a riser and a downcomer as in an air lift fermentor.
Separation procedures for the fermentation products, cells and/or chemicals, usually involve one or more of the following unit operations: centrifugation, extraction, distillation, filtration, ultrafiltration, crystallization and flocculation. Flotation is uncommon and usually considered a nuisance. It has been tried for the separation of proteins, including enzymes, and for the removal of microorganisms.
The present invention is broadly directed to a method of fermentation wherein the fermentation media is a stable nutrient media dispersion comprising a phase of microgas bubbles and a liquid phase. The microgas bubbles or bubble foam per se are known in the art; see U.S. Pat. No. 3,900,420 Sebba; however, this reference does not teach the use of the microgas bubbles as a part of the nutrient broth per se.
In one aspect of the invention, a fine dispersion (about 10.sup.-5 micron diameter bubbles) of a gas in a nutrient broth is provided. The dispersion provides an extremely large surface area per reactor volume for improved oxygen transfer to the microorganism, increased growth surfaces for the organisms, if needed, and a devide for flotation of fermentation products such as cells or the like; or a product for separations within the fermentor. Moreover, the invention makes use of the bubble foam, usually considered a nuisance or used merely for separations. The invention has lower air and power requirements than prior art systems such as stirred tank or tower fermenters. The foam can be used to harvest the microorganisms from the broth or for selective separation of products such as enzymes, antibiotics, proteins, cells and/or vitamins. The bubbles can be used as a catalyst by binding either microorganisms, enzymes or traditional catalysts to the surface. The advantages of the invention are increased oxygen transfer (or nutrient gas transfer) due to the very small bubble sizes, the coupling of the organism and/or substrate and catalyst to the bubble surface and simultaneous mixing, aeration and product and/or cell separation.
Broadly, the invention includes a method of fermentation which includes introducing a nutrient gas into a liquid nutrient formulation to create a stable nutrient media, to effect fermentation, comprising a liquid phase and a gaseous phase, the gaseous phase dispersed throughout the liquid phase to provide a foam-like medium. The bubble size of the gaseous phase is between about 0.1 to 200 microns and about 40-80% voids of the entire dispersion. Subsequently the fermentation products are separated from the dispersion.